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Non‐human primate fetal kidney transcriptome analysis indicates mammalian target of rapamycin (mTOR) is a central nutrient‐responsive pathway
Author(s) -
Nijland Mark J.,
SchlabritzLoutsevitch Natalia E.,
Hubbard Gene B.,
Nathanielsz Peter W.,
Cox Laura A.
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.122101
Subject(s) - transcriptome , biology , baboon , offspring , fetus , pi3k/akt/mtor pathway , kidney development , phenotype , kidney , in utero , pregnancy , kidney disease , medicine , endocrinology , signal transduction , microbiology and biotechnology , gene expression , gene , genetics , embryonic stem cell
Developmental programming is defined as the process by which gene–environment interaction in the developing organism leads to permanent changes in phenotype and function. Numerous reports of maternal nutrient restriction during pregnancy demonstrate altered renal development. Typically this alteration manifests as a reduction in the total number of glomeruli in the mature kidney of the offspring, and suggests that predisposition to develop chronic renal disease may include an in utero origin. In a previous study, we defined the transcriptome in the kidney from fetuses of control (CON, fed ad libitum ) and nutrient‐restricted (NR, fed 70% of CON starting at 0.16 gestation (G)) pregnancies at half‐way through gestation (0.5G), and established transcriptome and morphological changes in NR kidneys compared to CON. One goal of the present study was to use transcriptome data from fetal kidneys of CON and NR mothers at 0.5G with histological data to identify the molecular mechanisms that may regulate renal development. A second goal was to identify mechanisms by which NR elicits its affect on fetal baboon kidney. We have used an end‐of‐pathway gene expression analysis to prioritize and identify key pathways regulating the 0.5G kidney phenotype in response NR. From these data we have determined that the mammalian target of rapamycin (mTOR) signalling pathway is central to this phenotype.